Screening and Genetic Monitoring of Patients With Myelodysplastic Syndromes (MDS) Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University Medical Center Goettingen
Information provided by:
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
ClinicalTrials.gov Identifier:
NCT01355913
First received: May 17, 2011
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

In myelodysplastic syndromes (MDS) the knowledge about chromosomal aberrations is important for diagnosis, pathogenesis, prognosis and treatment. Usually, chromosomal anomalies in MDS patients are detected in bone marrow cells by chromosome banding analyses of metaphases. Alternatively or additionally they can be diagnosed by Fluorescence-in-Situ-Hybridization (FISH). The investigators here present a novel method for cytogenetic monitoring of MDS patients from peripheral blood which is representative for the clone size in bone marrow cells. The purpose of this prospective multicenter non-interventional diagnostic study is to detect and to follow chromosomal aberrations from peripheral blood closely, to assess karyotype evolution, to detect rare abnormalities and to correlate the molecular-cytogenetic results with peripheral blood counts, bone marrow morphology and treatment modalities and responses.


Condition
Myelodysplastic Syndromes (MDS)
Chromosmal Aberrations
Karyotype Evolution
Rare Abnormalities
Cytogenetic Monitoring

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Screening and Genetic Monitoring of Patients With MDS Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

Resource links provided by NLM:


Further study details as provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH:

Primary Outcome Measures:
  • Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells. [ Time Frame: The first FISH analysis is performed at the time of study entry (initial screening) and after that every 2 months in the first year and every 3 months in the second and third year. ] [ Designated as safety issue: No ]
    At each timepoint of FISH analysis the percentage of aberrant interphase nuclei is measured of all (at least 200) interphase nuclei counted.


Estimated Enrollment: 300
Study Start Date: October 2008
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Detailed Description:

Chromosomal aberrations in myelodysplastic syndromes (MDS) play a major role in diagnostics, pathogenesis, prognosis, and, more recently, in treatment allocations. Chromosomal anomalies can be detected by conventional chromosome banding analyses of bone marrow metaphases and most of them are provable by Fluorescence in situ hybridization (FISH) of circulating CD34+ progenitor cells from peripheral blood. For this prospective multicenter non-interventional diagnostic study sequential FISH analyses are performed on immunomagnetically enriched circulating CD34+ cells from peripheral blood as follows: A "super-panel" with the probes D7/CEP7, EGR1, CEP8, CEP XY, D20, p53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R (all Abbott® probes) is used for initial screening, every 12 months during follow-up and in every case of suspected progression. A smaller "standard-panel" with the probes EGR1, D7/CEP7, CEP8, p53, D20, CEP X/Y, TEL/AML1 - plus if necessary an informative probe of the superpanel- was performed for analyses at short intervals every 2 months in the 1st year and every 3 months during the 2nd and 3rd year. Peripheral blood counts are documented once a month, and full blood counts with the number of peripheral blasts are recommended at the time point of each FISH analysis. Bone marrow biopsies are not part of the study, but they are recommended to be performed every 6 to 12 months in the course of the disease. If a bone marrow biopsy is performed, conventional chromosome banding analyses on bone marrow metaphases and, additionally, FISH analyses of enriched CD34+ bone marrow cells and non-enriched bone marrow cells are performed. The results from peripheral blood are correlated with those of conventional banding and FISH analyses performed on bone marrow samples. The aims of this study are to detect acqired chromosomal aberrations in MDS patients from peripheral blood, to follow these anomalies by frequent analyses, to detect rare aberrations and to observe karyotype evolution from peripheral blood.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

20 ml of peripheral blood (pb) of a MDS patient are enriched by immunomagnetic cell sorting (by MACS® system). A FISH analysis is performed on these CD34+ cells according to product protocols using the FISH probe panels described above. The percentage of aberrant interphase nuclei (IN) is measured related to all (at least 200) IN counted. FISH analyses are performed every 2 months in the 1st and every 3 months in the 2nd and 3rd year of follow-up by the same method using the standard panel and, if necessary, an informative probe of the super panel. Pb counts are documented once a month, and full blood counts with peripheral blasts are recommended at the time point of each FISH analysis. Bone marrow (bm) biopsies are not part of the study, but they are recommended to be performed every 6 to 12 months. If a bm biopsy is performed, conventional chromosome banding analyses on bm metaphases and FISH analyses of enriched CD34+ and non-enriched bm cells are performed.

Criteria

Inclusion Criteria:

  • Clinical diagnosis (cytomorphologic proof) of primary or secondary myelodysplastic syndrome (MDS) or
  • Suspected myelodysplastic syndrome (MDS).
  • Age > 18 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355913

Locations
Germany
University Hospital Aachen
Aachen, Germany
University Hospital Dresden
Dresden, Germany
University Hospital Düsseldorf
Düsseldorf, Germany
Onkologikum
Frankfurt/Main, Germany
University Hospital Frankfurt/Main
Frankfurt/Main, Germany
University Medical Center Göttingen
Goettingen, Germany
Onkologische Kooperation Harz
Goslar, Germany
Group Practice Meyer/Ammon/Müller
Göttingen, Germany
Group Practice Uhle/Müller/Kröning/Jentsch-Ullrich
Magdeburg, Germany
Technical University Munich
Munich, Germany
Group Practice Schmidt/Galler/Klapthor
Munich, Germany
Group Practice Detken/Seraphin
Northeim, Germany
University Hospital Ulm
Ulm, Germany
Sponsors and Collaborators
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
University Medical Center Goettingen
Investigators
Study Chair: Detlef Haase, MD, Prof. University Medical Center Göttingen
  More Information

No publications provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Detlef Haase, University Medical Center Goettingen
ClinicalTrials.gov Identifier: NCT01355913     History of Changes
Other Study ID Numbers: Diagnostik-Studie
Study First Received: May 17, 2011
Last Updated: August 7, 2014
Health Authority: Germany: Ethics Commission

Keywords provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH:
Myelodysplastic syndromes (MDS)
chromosmal aberrations
cytogenetics
Fluorescence in situ hybridization (FISH)
CD34+ cells
peripheral blood

Additional relevant MeSH terms:
Congenital Abnormalities
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms

ClinicalTrials.gov processed this record on August 26, 2014